新一代修饰性醇抗真菌药物对抗多药耐药性白虫
Yiyuan Chen1, Yunxiao Li1, Kazi S Nahar1,2
1Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom.
Journal of medicinal chemistry
|June 23, 2025
概括
新的以醇为基础的化合物对耐药的Candida auris和其他真菌表现出强烈的活性. 这些新型抗真菌药物对抗性菌株有效,体内毒性低,为新的治疗提供了希望.
科学领域:
- 药用化学 医学化学
- 抗微生物耐药性 抗微生物耐药性
- 菌类学 菌类学是指菌类学.
背景情况:
- 抗真菌耐药性和有限的治疗选择需要开发新的药物类别.
- 由于其有限的治疗选择,Candida auris对全球健康构成重大威胁.
研究的目的:
- 开发具有强大的抗真菌活性的新型醇基化合物.
- 评估这些化合物对抗多抗药性真菌病原体的疗效,包括Candida auris.
主要方法:
- 合成新型的以醇为基础的化合物,其中包括循环异酸链接剂.
- 对各种Candida物种进行抗真菌敏感性测试 (MIC确定),包括耐醇菌株.
- 在体外测定CYP51抑制,生物膜消除和细胞内积累.
- 在 Galleria mellonella 和 Drosophila melanogaster 模型中进行了体内疗效和毒性研究.
主要成果:
- 几种新型醇化合物对Candida auris (MICs 0.0164μg/mL) 具有强烈活性,包括耐醇菌株.
- 化合物对其他Candida物种 (MICs <1μg/mL) 显示出广泛的活性.
- 化合物7,18和21的性能优于可纳;化合物7抑制了CYP51,消除了生物膜,并显示了增强的细胞内积累.
- 在体内研究表明,在5mg/kg时有效,但在50mg/kg时没有观察到毒性.
结论:
- 新型以醇为基础的化合物对抗多药耐药的Candida auris和其他病原性真菌有效.
- 化合物7表现出有希望的特性,包括CYP51抑制和生物膜消除.
- 开发的脚手架需要进一步研究,以治疗严重的真菌感染.
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